Mammalian epidermis is an ideal system in which to study stem cell behaviour as it is constantly being turned over, has a simple architecture, and is predominantly composed of a single cell lineage, the epidermal keratinocyte. Epidermis consists of layers of keratinocytes. Cells are continually shed from the epidermal surface and replaced by proliferation in the basal cell layer, raising the question of how epidermal homeostasis is achieved.

It has been argued the epidermis is maintained by long-lived, slowly-cycling stem cells, which in turn generate a short-lived population of transit-amplifying (TA) cells that differentiate after a limited number of cell divisions. We have recently reported that this "classical" stem/TA cell model is inconsistent with clonal fate data obtained through inducible genetic labelling in the tail skin of adult mice, which reveals a different mechanism of epidermal homeostasis. Murine epidermis is maintained by a single population of committed progenitor cells which behave stochastically, dividing to generate, on average, equal numbers of cycling or post-mitotic cells. The discovery of a new paradigm of stem-cell independent tissue maintenance in mouse raises the question as to whether similar rules may govern the behaviour of human keratinocytes.

In the basal layer of human interfollicular epidermis, near-quiescent stem cells are localised in a niche consisting of stem cell clusters, separated by proliferating and differentiating keratinocytes. Remarkably, this pattern is reconstituted in vitro. Combining a range of existing observations with new experimental data, we have elucidated the origin of patterning and quiescence in homeostatic tissue, and explained the ability of stem cells to reconstitute their niche in culture. Such behaviour points at a simple set of organisational principles controlling stem and progenitor cell fate, and provides a unified model of epidermal maintenance in mouse and human. In particular, we show that epidermis is maintained by a committed progenitor cell population whose stochastic behaviour enables stem cells to remain largely quiescent unless called upon for repair. These results raise questions as to the role of stem cells in other adult tissues.